CYP1A1-inducing Potency in H4IIE Cells and Chemical Composition of Technical Mixtures of Polychlorinated Biphenyls

Polychlorinated biphenyls (PCBs) are present in environmental and tissue samples as complex mixtures of dioxin-like and non-dioxin-like congeners. Induction of cytochrome (CYP) P4501A1-catalyzed 7-ethoxyresorufin-O-deethylase (EROD) activity in H4IIE hepatoma cells is widely used as a simple in vitro bioassay for the dioxin receptor-mediated biological action of dioxin-like agonists. Since the results of the assay may be influenced indirectly by abundant non-dioxin-like PCBs, its application to the bioanalysis of complex PCB mixtures was studied. In the PCB mixtures Arochlor 1254 and Clophen A50, potent dioxin-like non-ortho PCBs and polychlorinated dibenzofurans (PCDFs) were found in minor amounts. However, the non-ortho PCBs accounted for most of the overall 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents based on EROD induction (EROD-TEQs). A comparison with a pattern of toxic equivalents (TEQs) based on toxic equivalency factors (I-TEFs) recently suggested in an international report revealed a much higher relative impact of mono-ortho PCBs on I-TEQs than on EROD-TEQs while total EROD-TEQs approximately coincided with total I-TEQs. It is concluded that the H4IIE bioassay is useful to assess total I-TEQs but does not reflect the individual contributions of PCB subgroups because of a higher evaluation of mono-ortho and di-ortho PCBs by I-TEFs. Based on individual EROD-TEFs, slightly higher mean EROD-TEQs than those calculated by assuming additive behaviour of single PCBs were obtained. This finding suggests a minor synergistic influence of non-dioxin-like PCBs on the inducing potency of dioxin-like agonists in the H4IIE bioassay.